A robust and interpretable gene signature for predicting the lymph node status of primary T1/T2 oral cavity squamous cell carcinoma.

Overview

abstract

Oral cavity squamous cell carcinoma (OSCC) affects more than 30,000 individuals in the US annually, with smoking and alcohol consumption being the main risk factors. Management of early stage tumors usually includes surgical resection followed by postoperative radiotherapy in certain cases. The cervical lymph nodes (LN) are the most common site for local metastasis and elective neck dissection is usually performed if the primary tumor thickness is greater than 3.5 mm. However, postoperative histological examination often reveals that many patients with early stage disease are negative for neck nodal metastasis, posing a pressing need for improved risk stratification to either avoid over-treatment or prevent the disease progression. To this end, we aimed to identify a primary tumor gene signature that can accurately predict cervical LN metastasis in patients with early stage OSCC. Using gene expression profiles from 189 samples, we trained K-top scoring pairs (K-TSPs) models and identified six gene pairs that can distinguish primary tumors with nodal metastasis from those without metastasis. The signature was further validated on an independent cohort of 35 patients using RT-PCR in which it achieved an Area Under the ROC Curve (AUC) and accuracy of 90% and 91% respectively. These results indicate that such signature holds promise as a quick and cost effective method for detecting patients at high risk of developing cervical LN metastasis, and may be potentially used to guide the neck treatment regimen in early-stages OSCC. This article is protected by copyright. All rights reserved.